OLALIAMID PROTECTS OBESE DOGS. DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY

Canine obesity is a common nutritional disease, progressively increasing in western countries over the years. In overweight dogs, quality of life is poor and lifespan is shortened; furthermore, canine obesity can predispose to the development of specific pathologies. The present study aimed to investigate whether an olive oil derivative enriched in N-acyl-ethanolamines (Olaliamid, OLA) [1] may protect dogs against obesity-induced metabolic and cardiovascular changes. After obtaining the owner’s written consent, 24 dogs aged 2-10 years, weighting ≥ 4.5 kg and with body condition score (BCS) ≥ 7/9 were included, provided they were otherwise healthy. The dogs received a commercial maintenance diet no later than two weeks before enrollment and their lifestyle remained unchanged throughout the study. According to a computer-generated randomization list, dogs were divided in two groups: one supplemented with the study product (OLA) and the other with placebo (OLA vehicle), packaged in indistinguishable bottles. The product was administered once a day orally for 3 months at 0.7 ml/5kg body weight (BW). At baseline (V0) and 3 months later (V1), dogs underwent physical examination and echocardiography (Mindray DC-90, Cina), while owners were administered an 8-item questionnaire on a 10-cm visual analog scale (VAS) about their dog’s general condition. The thickness of the interventricular septum (IVSdN) and the posterior wall of the left ventricle (LV) in end-diastole (LVPWdN), as well as the internal dimensions of the LV (LVIDdN and LVIDdsN), were measured in M-mode and normalized for BW. At each time point, blood samples were collected and processed immediately for biochemical analyses, or stored in aliquots at −80 °C until batch assay for leptin (Millipore, USA), IL-6 (Genorise, USA), Reactive Oxygen Metabolites (d-ROMs) and biological antioxidant potential (BAP) (Diacron, Italy). The study was approved by the Ethical Committee of the University of Naples Federico II (PG/2021/0119942). Generalized linear mixed model with Tukey-Kramer post-hoc test for multiple comparisons was used to compare changes between groups, while t-test to compare changes within group at different times. The signed rank test was preferred for robustness in the presence of outliers. P was set at <0.05. The mean age of dogs was 7.5 years, while mean BW was 26.3 ± 13 SD kg. Groups were homogenous at baseline. According to dog owners, difficulty rising from lying down significantly increased in the placebo (P=0.035) but not in the OLA group. No differences were observed in BW and BCS between or within groups. A significant difference was observed in serum ALT (P=0.005), whose level decreased by 20% in the OLA group, while increased by 16% in the placebo group. Similar results were observed for azotaemia (P=0.051); furthermore, bilirubin decreased in the OLA (P=0.030) but not in the placebo group. OLA exerted an anti-inflammatory and antioxidant effect, since it counteracted the increase in leptin observed in the placebo group (P=0.011), decreased IL-6 (P=0.042) and d-ROMs (P = 0.008), and increased BAP compared to the placebo group (P=0.032). Finally, OLA showed a cardioprotective effect, with a significant decrease of IVSdN (P=0.028), LVPWdN (P=0.047), IVSd/LVIDd (P=0.015) and LVPWd/LVIDd (P=0.034) vs placebo. Overall, our data showed that OLA was effectiveness against obesity-induced meta-inflammation and oxidative stress, as well as metabolic and cardiovascular dysfunctions.